NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY VERSUS PERICENTRAL RETINAL DEGENERATION PHENOTYPE: WHICH CAME FIRST? A CASE REPORT.

PURPOSE: To report a case of nonparaneoplastic autoimmune retinopathy with phenotypical features of pericentral retinal degeneration (PRD) who responded to IV immunoglobulin therapy. METHODS: A case report. A 27-year-old man presented with recent subacute progressive nyctalopia and photopsia. RESULTS: Dilated fundoscopy demonstrated confluent yellow-white patches along the main temporal vascular arcades with sparing of the central island in the posterior pole. Color vision, fundus autofluorescence, fluorescein angiography, static visual field, and electroretinographic studies were inconclusive for retinal degeneration. Subsequent genetic testing for known mutations was negative. Workup for paraneoplastic autoimmune retinopathy was negative. Antiretinal antibodies were positive. The patient was diagnosed with nonparaneoplastic autoimmune retinopathy and was treated with IV immunoglobulin, which resulted in objective and subjective improvement on electroretinography, visual field, and optical coherence tomography of the retina. CONCLUSION: Nonparaneoplastic autoimmune retinopathy may present in a patient with the clinical phenotype of PRD. It is essential to rule out nonparaneoplastic autoimmune retinopathy in patients with subacute changes in the natural course of pericentral retinal degeneration because treatment with IV immunoglobulin may be helpful.

Late recurrence in birdshot chorioretinopathy.

OBJECTIVE: To compare the demographic, clinical, ancillary testing, and multimodal imaging characteristics of birdshot chorioretinopathy (BSCR) patients with late recurrence and birdshot patients with durable remission. PATIENTS AND METHODS: This was a retrospective observational case series. The above-mentioned parameters were studied in BSCR patients with late recurrence (group 1) and BSCR patients with durable remission (group 2). RESULTS: Fifty-five patients were included in this study. The average age of patients was 62.1 ± 11.1 years (range, 35-88 years). Groups 1 and 2 included 20 (36.4%) and 35 (63.6%) patients, respectively. In group 1, the average age of patients was 60.5 ± 10.39 years (range, 35-79 years). The female-to-male ratio was 16:4. In group 2, the average age of patients was 63.1 ± 11.6 years (range, 37-88 years). The female-to-male ratio was 22:13. None of the demographic, clinical, ancillary testing, and multimodal imaging parameters were statistically significantly different between the two groups. Using a receiver operating characteristics (ROC) curve, we found that the ideal duration of successful therapy to induce durable remission was 30 months with 70% sensitivity and 40% specificity (ideal point on the curve). A Kaplan-Meier survival curve demonstrated that late recurrence was seen within 30 months after stopping successful treatment of patients with BSCR. CONCLUSION: There are no demographic, clinical, ancillary testing, or multimodal imaging characteristics that can predict late recurrence in BSCR patients. However, we found that 30 months of successful treatment may be ideal and recommended.

Effects of Subcutaneous Repository Corticotropin Gel Injection on Regulatory T Cell Population in Noninfectious Retinal Vasculitis.

AIM: To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis. PATIENTS AND METHODS: Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study. RESULTS: Eighteen patients (33 eyes) were included in the study. Eleven (61.1%) patients [20 (60.6%) eyes] and 7 (38.9%) patients [13 (33.3%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found. CONCLUSION: RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.

Birdshot Chorioretinopathy: Resistant versus Responsive.

PURPOSE: To search findings that can explain the heterogeneity between Resistant and Responsive patients with birdshot chorioretinopathy. PATIENTS AND METHODS: This was a retrospective observational case series on "Responsive" versus "Resistant" birdshot chorioretinopathy. RESULTS: One-hundred-eighty and Ninety-nine patients were included in the Responsive and Resistant groups respectively. Multivariate analysis of paraclinical variables at the first visit demonstrated that mean deviation (p = .04), pattern standard deviation (p < .001), optic nerve head leakage (p = .012), large vessel leakage and staining (p = .01), and macular small vessel leakage (p = .03) were statistically significantly different between the two groups; however, at the visit preceding successful therapy, only macular small vessel leakage (p = .01) was statistically significantly different between the two groups. CONCLUSION: .Small vessel leakage in the macular area and/or optic nerve head leakage at the earliest visit might be risk factors for resistant birdshot chorioretinopathy.

Ocular Mucus Membrane Pemphigoid: A Primary Versus Secondary Entity.

PURPOSE: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). METHODS: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. RESULTS: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. CONCLUSIONS: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.

Acute macular neuroretinopathy in a patient with birdshot chorioretinopathy after intravitreal triamcinolone suspension injection.

PURPOSE: To report a case of acute macular neuroretinopathy (AMN) after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema secondary to birdshot chorioretinopathy. METHOD: A case report. PATIENT: A 62-year-old female. RESULTS: The patient presented with acutely decreased vision and a ring scotoma around her central vision three days after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema in her right eye (OD) secondary to birdshot chorioretinopathy. She had undergone pars plana vitrectomy, cataract extraction, and secondary intraocular lens implantation OD three months prior to the recent injection. Best-corrected visual acuity (BCVA) was 20/1000 OD and 20/50 OS. Intraocular pressure was 21 mmHg OD and 12 mmHg OS. Fluorescein angiography demonstrated a hypofluorescent area in the perifoveal zone OD. Optical coherence tomography OD depicted hyperreflective areas in the outer nuclear layer, outer plexiform layer, and retinal pigment epithelium. We diagnosed her with AMN OD and started her on brimonidine three times a day OD. She came back a week later with resolved scotoma and her vision improved to 20/60 OD. Five weeks later, BCVA was 20/40 and Intraocular pressures (IOP) was 12 mmHg OD. CONCLUSIONS AND IMPORTANCE: Intravitreal triamcinolone injection may be a cause of AMN with cystoid macular edema (CME) and borderline-high intraocular pressure. Brimonidine may be an effective treatment for these patients in the early course of the disease.

Elevated serum BAFF in patients with ocular cicatricial pemphigoid.

OBJECTIVE: The efficiency of B-cell depletion therapy for severe ocular cicatricial pemphigoid (OCP) highlights the key role of B lymphocytes in the immunopathogenesis of OCP. B-cell activating factor (BAFF) is a potent B-cell growth factor and costimulator of immunoglobulin production. Elevated serum BAFF is associated with systemic autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and bullous pemphigoid. We hypothesize that serum BAFF levels are also increased in patients with OCP. METHODS: Sera were collected from 30 patients with new-onset active OCP, 9 with disease in remission, 10 with OCP relapse, and 15 healthy control individuals. An enzyme-linked immunosorbent assay was performed to measure the concentration of serum BAFF. RESULTS: BAFF was significantly higher in patients with new-onset active OCP (700.8 ± 181.8 pg/mL) than in healthy control individuals (564.1 ± 133.2 pg/mL; p = 0.014). No significant difference was found between patients with OCP in remission (585.4 ± 216.2 pg/mL) and healthy control individuals. Patients with disease relapse treated with rituximab had an extremely high concentration of BAFF (1721.9 ± 790.8 pg/mL). Longitudinal analysis of serum BAFF from 6 patients showed that BAFF decreased as the disease went from new onset (895.0 ± 240.8 pg/mL) to remission (625.4 ± 199.8 pg/mL; p = 0.003). CONCLUSIONS: BAFF is involved in the active inflammation of OCP. Targeting BAFF with an antagonist may be therapeutically beneficial for patients with refractory OCP, especially those resistant to rituximab.

Diagnostic and Prognostic Roles of Serum Interleukin-6 Levels in Patients with Uveitis.

PURPOSE: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. METHODS: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. RESULTS: Mean IL-6 level was 1.77 ± 0.97 pg/ml and 10.2 ± 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant (p = .015, p = .000, p = .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83, p < .001), Age (OR = 0.95, p = .03) and number of flare-ups (OR = 2.9, p = .02). CONCLUSION: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.

Fixed-Luminance and Multi-Luminance Flicker Electroretinography Parameters in Patients with Early Active Birdshot Chorioretinopathy.

PURPOSE: To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy. METHODS: Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group. RESULTS: There was no statistically significant difference between the Fixed-Luminance flicker magnitude (P = .6), the Fixed-Luminance flicker phase (P = .9), and the Multi-Luminance flicker phase area under the curve (P = .55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. (P = .003). CONCLUSIONS: Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease. ABBREVIATIONS: BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m2: Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry.

Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis.

PURPOSE: The therapeutic use of the RPE-neuropeptide α-MSH suppresses experimental autoimmune uveitis (EAU). This suppression is partially through the α-MSH melanocortin 5 receptor (MC5r). Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of phagolysosome-activation in macrophages following α-MSH-treatment of EAU. METHODS: The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r(-/-) mice were used to treat macrophages to assay for phagolysosome activation. RESULTS: MC5r(-/-) mice treated with α-MSH recovered from EAU, but with greater retinal damage, and the RPE suppressed phagolysosome activation in wild type but not in MC5r(-/-) macrophages. In addition, α-MSH did not suppress phagolysosome activation in MC5r(-/-) macrophages, and resting-MC5r(-/-) macrophages had augmented phagocytic activity. CONCLUSION: α-MSH treatment of EAU mediates a MC5r-dependent recovery of RPE suppression of phagolysosome activation in macrophages possibly altering antigen processing and presentation. Also, MC5r-expression helps protect the retina from inflammatory damage. In addition, MC5r-expression is important in the homeostatic maintenance of phagosome-maturation within macrophages.

Response to the Second TNF-α Inhibitor (Adalimumab or Infliximab) after Failing the First One in Refractory Idiopathic Inflammatory Retinal Vascular Leakage.

PURPOSE: To determine the response to the second TNF-α inhibitor (adalimumab and infliximab) after failing the first agent in idiopathic inflammatory retinal vascular leakage. MATERIALS AND METHODS: This was a retrospective observational case series. Patients with the diagnosis of idiopathic inflammatory retinal vascular leakage who had received both infliximab and adalimumab were included in the study. RESULTS: Twelve and 15 patients received adalimumab (Group one) and infliximab (Group two) as the first treatment, respectively. The remission rates between Group one (58.3%) and Group two (66.7%) were not statistically significant. (P = .4) As the second agent, adalimumab was more effective in younger patients (27.5 ± 20.6) compared to older patients (48.75 ± 10.2). (P = .03). Moreover, patients with lower vision responded marginally better to infliximab as the second treatment (P = .06). CONCLUSION: Either TNF-α inhibitor, adalimumab and infliximab, can be employed in the treatment of the patients with idiopathic inflammatory retinal vascular leakage who fail one of these agents.

Clinical features, visual outcome, and poor prognostic factors in occlusive retinal vasculitis.

OBJECTIVE: To investigate the clinical features, treatment, and visual outcome of occlusive retinal vasculitis (ORV), with a focal analysis on prognostic factors associated with poor visual outcome. METHODS: We conducted a retrospective cohort study in patients diagnosed with ORV with at least 6 months of follow-up. Demographic data, ocular features, best corrected visual acuity (BCVA), fluorescein angiography, therapy regimens, and outcomes were collected from the Massachusetts Eye Research and Surgery Institution database from 2006 to 2017. Multivariate logistic regression was performed to analyze the factors independently predicting poor visual outcome. RESULTS: Fifty-two patients (69 eyes) were enrolled, 42 with noninfectious cause, 9 with infectious cause, and 1 with masquerade uveitis. Systemic inflammatory diseases, including necrotizing vasculitis, sarcoidosis, multiple sclerosis, systemic lupus erythematosus, and Behçet's disease comprised the causes of ORV. Forty of the 42 patients with noninfectious ORV received immunomodulatory therapy (IMT), and 35 patients (87.5%) were able to achieve steroid-free remission. Compared with the BCVA at the initial visit (0.66 [±0.11] logMAR), there was significant improvement at the most recent visit (0.37 [±0.07] logMAR, p = 0.001). A multivariate analysis demonstrated that optic nerve atrophy, macular ischemia, and poor BCVA at initial presentation were independently correlated with poor visual outcome. CONCLUSIONS: ORV could be caused by a wide spectrum of systemic inflammatory diseases. Aggressive IMT is preferred to achieve a steroid-free durable remission for noninfectious ORV. Optic nerve atrophy, macular ischemia, and poor BCVA at the initial visit predict a poor visual outcome.

Acquired Vitelliform-Like Lesion in Uveitis: A case-series.

PURPOSE: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p = .005), the presence of vasculitis (p = .01), the presence of active choroiditis (p = .01), and the presence of CME on OCT (p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p < .001) and the last follow-up visit (p = .014) in the AVLL group. CONCLUSION: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.

Pediatric uveitis: A comprehensive review.

Pediatric uveitis accounts for 5-10% of all uveitis. Uveitis in children differs from adult uveitis in that it is commonly asymptomatic and can become chronic and cause damage to ocular structures. The diagnosis might be delayed for multiple reasons, including the preverbal age and difficulties in examining young children. Pediatric uveitis may be infectious or noninfectious in etiology. The etiology of noninfectious uveitis is presumed to be autoimmune or autoinflammatory. The most common causes of uveitis in this age group are idiopathic and juvenile idiopathic arthritis-associated uveitis. The stepladder approach for the treatment of pediatric uveitis is based on expert opinion and algorithms proposed by multidisciplinary panels. Uveitis morbidities in pediatric patients include cataract, glaucoma, and amblyopia. Pediatric patients with uveitis should be frequently examined until remission is achieved. Once in remission, the interval between follow-up visits can be extended; however, it is recommended that even after remission the child should be seen every 8-12 weeks depending on the history of uveitis and the medications used. Close follow up is also necessary as uveitis can flare up during immunomodulatory therapy. It is crucial to measure the impact of uveitis, its treatment, and its complications on the child and the child's family. Visual acuity can be considered as an acceptable criterion for assessing visual function. Additionally, the number of cells in the anterior chamber can be a measure of disease activity. We review different aspects of pediatric uveitis. We discuss the mechanisms of noninfectious uveitis, including autoimmune and autoinflammatory etiologies, and the risks of developing uveitis in children with systemic rheumatologic diseases. We address the risk factors for developing morbidities, the Standardization of Uveitis Nomenclature (SUN) criteria for timing and anatomical classifications, and describe a stepladder approach in the treatment of pediatric uveitis based on expert opinion and algorithms proposed by multi-disciplinary panels. In this review article, We describe the most common entities for each type of anatomical classification and complications of uveitis for the pediatric population. Additionally, we address monitoring of children with uveitis and evaluation of Quality of Life.

COVID-19 Recombinant mRNA Vaccines and Serious Ocular Inflammatory Side Effects: Real or Coincidence?

PURPOSE: To report two cases; bilateral arteritic anterior ischemic optic neuropathy (AAION) and bilateral acute zonal occult outer retinopathy (AZOOR) after COVID-19 mRNA vaccination. CASE REPORT: The first patient was a 79-year-old female was presented to us 35 days after a sudden bilateral loss of vision, which occurred two days after receiving the second recombinant mRNA vaccine (Pfizer) injection. Temporal artery biopsy was compatible with AAION. At presentation, the best-corrected visual acuity was 20/1250 and 20/40 in the right and left eyes on the Snellen acuity chart, respectively. There was 3+ afferent pupillary defect in the right eye. The anterior segment and posterior segment exams were normal except for pallor of the optic nerve head in both eyes. Intraocular pressure was normal in both eyes. She was diagnosed with bilateral AAION and Subcutaneous tocilizumab 162 mg weekly was recommended with monitoring her ESR, CRP, and IL-6.The second patient was a 33-year-old healthy female who was referred to us for a progressive nasal field defect in her left eye, and for flashes in both eyes. Her symptoms started 10 days after receiving the second recombinant mRNA vaccine (Moderna) injection. Complete bloodwork performed by a uveitis specialist demonstrated high ESR (25) and CRP (19) levels. As a result, she was diagnosed with unilateral AZOOR in her left eye and was subsequently treated with an intravitreal dexamethasone implant in the same eye. At presentation, vision was20/20 in both eyes. The anterior segment and posterior segment exams were completely normal except for the presence of abnormal white reflex in the temporal macula of her left eye. We diagnosed her with bilateral AZOOR. Since she was nursing, intravitreal dexamethasone implant was recommended for the right eye. CONCLUSION: There may be a correlation between ocular inflammatory diseases with autoimmune mechanism and the mRNA COVID-19 vaccination.

Chlorambucil combination therapy in refractory serpiginous choroiditis: A cure?

PURPOSE: To find a remedy for serpiginous choroiditis refractory to oral prednisone and chlorambucil treatment. OBSERVATIONS: Eight eyes of four patients (all female) with advanced macular involvement secondary to serpiginous choroiditis were included in the study. The average age of the patients was 45.2 years. One eye of each patient was legally blind and the lesion was close to the fovea in the other eye. All four patients failed oral prednisone and chlorambucil therapy. However, case 1 responded to chlorambucil treatment after intravitreal dexamethasone implant implantation and discontinuation of oral prednisone. Case 2 responded to chlorambucil therapy when oral prednisone was stopped in combination with infliximab therapy. Due to long follow-up period of more than four years, these two cases are considered to be cured. Case 3 and case 4 were not able to achieve remission with chlorambucil and immunomodulatory therapy. They refused intravitreal steroid implant due to side effects profile. CONCLUSIONS AND IMPORTANCE: The stability of WBC counts within toxic levels close to normal or lower limits of normal (3000-4500 cells/µl) during treatment with chlorambucil is an essential factor for the success of this therapy. A combination of dexamethasone intravitreal implant with chlorambucil therapy can be an effective and promising regimen in inducing and maintaining remission in refractory serpiginous choroiditis patients who fail a combination of systemic corticosteroid and chlorambucil therapy.

Vascular abnormalities in uveitis.

Inflammation can involve several ocular structures, including the sclera, retina, and uvea, and cause vascular changes in these tissues. Although retinal vasculitis is the most common finding associated with uveitis involving the posterior segment, other vascular abnormalities may be seen in the retina. These include capillary nonperfusion and ischemia, vascular occlusions, preretinal neovascularization, microaneurysms and macroaneurysms, and telangiectasia. Moreover, vasoproliferative tumors and subsequent coat-like response can develop secondary to uveitis. Fluorescein angiography is ideal for the investigation of retinal vascular leakage and neovascularization, while optical coherence tomography angiography can provide depth resolved images from the superficial and deep capillary plexus and can demonstrate vascular remodeling. Choroidal vascular abnormalities primarily develop in the choriocapillaris or in the choroidal stroma and can appear as flow void in optical coherence tomography angiography and filling defect and vascular leakage in indocyanine green angiography. Extensive choriocapillaris nonperfusion in the presence of choroidal inflammation can increase the risk of choroidal neovascular membrane development. Iris vascular changes may manifest as dilation of vessels in stroma due to inflammation or rubeosis that is usually from ischemia in retinal periphery secondary to chronic inflammation. More severe forms of scleral inflammation, such as necrotizing scleritis, are associated with vascular occlusion in the deep episcleral plexus, which can lead to necrosis of sclera layer and uveal exposure.

Tocilizumab Employment in the Treatment of Resistant Juvenile Idiopathic Arthritis Associated Uveitis.

AIM: To determine the efficacy and safety of intravenous tocilizumab in refractory juvenile idiopathic arthritis associated uveitis. PATIENTS AND METHODS: This was a retrospective observational case series. Patients with refractory juvenile idiopathic arthritis associated uveitis, who had received tocilizumab were included in this study. RESULTS: 8 patients (14 eyes) were included in this study. The average age of the patients at the first visit was 16.8 ± 11.2 years (7-40). The average duration of follow-up period after starting treatment was 28.6 ± 24.6 months (9-70). Intravenous tocilizumab infusions induced and maintained remission in 5 patients (8 eyes). Vasculitis was resolved within 8 months in all but one patient. The presence of papillitis before starting treatment was directly correlated with visual acuity improvement. No side effects were observed. CONCLUSION: Intravenous tocilizumab infusion can be an effective and safe method of treatment to induce and maintain remission in resistant juvenile idiopathic arthritis associated uveitis.